Combined administration of a non-neurotoxic 3,4-methylenedioxymethamphetamine analogue with amphetamine produces serotonin neurotoxicity in rats
- PMID: 1717873
- DOI: 10.1016/0028-3908(91)90192-e
Combined administration of a non-neurotoxic 3,4-methylenedioxymethamphetamine analogue with amphetamine produces serotonin neurotoxicity in rats
Abstract
In the present study, a central serotonin neurotoxicity was induced by combining a non-neurotoxic 3,4-methylenedioxymethamphetamine analogue, 5-methoxy-6-methyl-2-aminoindan (MMAI), with the non-vesicular dopamine (DA) releaser, S-(+)-amphetamine (Amp). With the multiple dosing regimen utilized neither drug alone resulted in any changes in serotonergic parameters, including 5-HT, 5-HIAA and the number of 5-HT uptake sites. However, MMAI (10 mg/kg) in combination with Amp (2 x 2.5 mg/kg) did result in a long-term 20% decrease in cortical serotonergic parameters. The same dose of Amp plus 20 mg/kg MMAI resulted in a 50 to 60% reduction. Effects in the hippocampus and caudate nucleus were similar. These data support the hypothesis that DA release plays a critical role in the serotonin neurotoxicity of substituted amphetamines.
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